3D Bioprinting of Gradient Scaffolds with Biomimetic Capillaries for Osteochondral Regeneration

Nanyang Technological University, Singapore

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Abstract

Osteochondral defects pose significant clinical challenges owing to the complex hierarchical tissue structure and the limited intrinsic regenerative capacity of cartilage. Existing strategies remain constrained by interfacial stress concentration, insufficient vascularization, or both. This study develops a 3D bioprinting strategy that simultaneously integrates continuous gradient scaffolds with biomimetic capillary networks for osteochondral regeneration. The bioinks were formulated with sodium alginate, methylcellulose, and gellan gum as the hydrogel matrix, with Pluronic F127 serving as a thermosensitive fugitive material for vascular channel fabrication. Mesenchymal stem cells, chondrocytes, and osteoblasts were encapsulated for region-specific bioprinting. The gradient scaffolds exhibited porosity ranging from 82.3 ± 3.7% in cartilage regions to 65.8 ± 4.2% in bone regions, with compressive modulus spanning from 0.8 to 68.5 MPa, closely mimicking native tissue properties. Biomimetic vascular networks achieved 95.6 ± 2.1% channel connectivity, facilitating effective nutrient transport. Cell viability exceeded 87% across all regions, and region-specific gene expression was upregulated by 3.2 to 6.3 folds for chondrogenic and osteogenic markers. Functional biological outcomes were confirmed by extracellular matrix deposition, endothelial cell monolayer formation within vascular channels with 89.3 ± 4.2% positive expression of CD31 and VE-cadherin, and controlled release of angiogenic growth factors that promoted in vitro tube formation. The interfacial shear strength of 4.2 ± 0.6 MPa eliminated stress concentration at the cartilage-bone transition. These findings establish a foundation for bioprinted osteochondral constructs with integrated vascularization, and future work will prioritize in vivo validation in animal defect models.